1. Field of the Invention
This invention relates to an aqueous solution of nitroglycerin.
2. Description of the Prior Art
Nitroglycerin, which has been used as a medicine against angina pectoris for more than 100 years, is still an important medicine for curing circulatory diseases, such as angina pectoris, cardiac asthma, and cerebral anemia due to local angiospasm. Although this medicine has usually been used in the form of a tablet, much attention has recently come to be directed to the use thereof in the form of an injectable solution which permits easier control of each dose, as it has begun to be employed for treating cardiac infarction or unsufficiency, and for hypotensive anesthesia during a surgical operation.
Various methods have hitherto been proposed for preparing an injectable solution of nitroglycerin, i.e., an aqueous solution thereof [Ho-Leung Fung, Am. J. Hosp. Pharm., vol. 35, 528 (1978)]. For example, the following methods are known:
(1) Water is added to a solution of nitroglycerin in ethanol or propylene glycol to form an aqueous solution of nitroglycerin;
(2) Lactose powder is caused to adsorb nitroglycerin, and dissolved in water;
(3) A commercially available sublingual tablet of nitroglycerin is dissolved in water, and insoluble impurities are removed by filtration; and
(4) Nitroglycerin is directly dissolved in water.
The method as indicated at (1) above, however, involves a number of disadvantages which are due to the presence of ethanol or propylene glycol. Due to its decomposition caused by such an organic solvent, nitroglycerin has a low degree of stability for storage which makes it difficult to guarantee the quality of the injectable solution. The presence of such a solvent also complicates the pattern in which the medicine takes effect.
Referring to the method as indicated at (2) above, nitroglycerin in this method has a low degree of stability for storage due to the presence of lactose. Moreover, it is difficult to obtain any lactose warranted for the absence of any pyrogen and the presence of antigenicity, since the lactose according to the Japanese Pharmacopoeia is intended for internal or external use, and not for injection. Therefore, it is difficult to prepare an injectable solution of nitroglycerin by using any commercially available lactose.
The method (3) above is not a method which is suitable for manufacturing an injectable solution of nitroglycerin on an industrial basis. The use of a commercial end product as starting material leads to an increase in the cost of manufacture. It is not possible to avoid the inclusion of an ingredient or ingredients of the tablet which are not approved for use in an injection; therefore, nitroglycerin has a low degree of stability for storage when this method is used to prepare the injectable solution. Moreover, it is impossible to avoid the possibility of any pyrogen being included in the injectable solution.
As opposed to these methods, the method (4) above can be employed for preparing an injectable solution in which nitroglycerin maintains a satisfactory degree of stability for storage. As nitroglycerin is a highly explosive substance, however, it is impossible to transport it to a place where medicines are manufactured. Moreover, as nitroglycerin is not easily soluble in water, it is likely to explode during its dissolution, and a long time is required for the complete dissolution of nitroglycerin in water. This is definitely a factor which may result in promoting inclusion of any pyrogen which must be avoided for the manufacture of an intravenous injectable solution.